Drug abuse or dependence is extremely in common in patients with bipolar disorder and is associated with increased rates of hospitalization, poor outcome during hospitalization, violence towards self and others, and nonadherence to bipolar disorder treatment. The abuse of cocaine and other stimulants is particularly common in patients with bipolar disorder. However, minimal data are available on the treatment of these patients. No randomized, controlled trials published, to date, have specifically examined the treatment of persons with bipolar disorder and cocaine dependence. Our group has developed a research program that evaluates medications for persons with bipolar disorder and substance dependence. A particularly promising medication that we have investigated is citicoline, an agent that modulates cholinergic systems and membrane phospholipid metabolism. Our randomized, placebo-controlled pilot data from 44 participants suggested that citicoline is very well tolerated and was associated with a statistically significant reduction in cocaine use and improvement in measures of cognition in patients with bipolar disorder and cocaine dependence. Based on these promising but preliminary findings a larger, definitive trial is proposed. This application proposes a 12-week randomized, double-blind, placebo-controlled, add-on trial of citicoline (2000 mg/day) in 130 outpatients with bipolar I disorder and cocaine dependence. Participants will be evaluated three times each week for cocaine use with urine drug screens, weekly for assessment of self- reported cocaine use and craving, and weekly for depressive and manic/hypomanic symptom severity. Executive functioning, attention, and working and declarative memory will be assessed at baseline and weeks 3, 6, and 12. Medication adherence will be monitored by self-report and with metered dosing caps. Manual- based cognitive-behavioral therapy specifically designed for people with bipolar disorder and substance abuse will be provided to both treatment groups. Concomitant medication changes, when necessary, will be managed using a treatment guideline. We hypothesize that citicoline therapy will be associated with decreased cocaine use and improvement in cognition. To conduct this trial we have assembled a research team with expertise in mood disorders, clinical trials, cocaine dependence, neuropsychological testing, and statistical analysis. [unreadable] [unreadable] [unreadable]